Antiplatelet Therapy in HIV

September 13, 2018 updated by: NYU Langone Health

Antiplatelet Therapy in HIV - Antiplatelet and Immune Modulating Effects of Aspirin or Clopidogrel in Subjects With HIV

The proposed study will add to the growing understanding of platelet activity and platelet inhibition in subjects with HIV. It will examine the relationship between platelet activity and its inhibition by antiplatelet therapy (aspirin monotherapy and clopidogrel monotherapy) in this high-risk cohort. Furthermore, it will provide important data on the mechanism of platelet activity and its inhibition using biomarkers of platelet activity, inflammation, immune activity and endothelial function and genetic expression profiling.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

There is substantial evidence that the risk of serious non-AIDS conditions, such as cardiovascular disease, kidney disease, liver disease, and non-AIDS-defining malignancies, is increased in persons with HIV infection as compared to the general population. HIV-induced activation of inflammatory and coagulation pathways have been implicated in this increased risk. However, causative mechanisms linking HIV, inflammation, and increased risk of non-AIDS diseases are poorly described. The investigators are interested in studying the link between HIV induced inflammation and cardiovascular disease. Inflammation mediates many aspects of disease pathogenesis in atherosclerosis, involving diverse cell types and mediating signals. Specifically, platelets have been implicated in atherosclerosis because of their pro-inflammatory and thrombogenic effects. Moreover, clinical studies have demonstrated the importance of platelet activity in coronary artery atherosclerosis and thrombosis. Whereas there is a great understanding of the pathogenesis of cardiac disease, there is a wide knowledge gap in the understanding of mechanisms of cardiovascular disease in patients with HIV.

A recent study by the investigators demonstrated that platelet activity is heightened in subjects with HIV. Following 1-week of low-dose aspirin, platelet activity was inhibited. A surprising finding of this study demonstrated that antiplatelet therapy with 1 week of aspirin (325mg dose x1 day followed by 81mg daily) improved immune activity in subjects with HIV. The current study is being performed to replicate those findings when compared with a control group. Moreover, it remains unknown if the finding was specific to aspirin or whether the results were attributed to the antiplatelet effect of the drug. Clopidogrel is another antiplatelet therapy that targets the P2Y12 receptor (a different mechanism than aspirin) that has been shown to lower the risk of cardiovascular events in various clinical settings. The doses of aspirin and clopidogrel the investigators will be employing have been tested in hundreds of studies with well-known benefits and risks. The investigators believe that understanding the mechanistic role of platelet inhibitors in the setting of HIV will help uncover a new strategic pathway of HIV pathogenesis. Also, subjects with HIV are at increased risk for cardiovascular events and understanding the platelet inhibition of aspirin and clopidogrel will help establish better designs for future trials aimed at preventing these events in HIV infected persons.

The investigators have demonstrated that platelet activation is increased in HIV infection and can be attenuated by low-dose aspirin in a non-randomized study without a control group. Therefore, the Specific Aims of the study to be established are as follows:

  • The effect of aspirin versus control on markers of platelet activity, inflammation, immune activity, and endothelial function.
  • The effect of Clopidogrel versus control on markers of platelet activity, inflammation, immune activity, and endothelial function.

Study Type

Interventional

Enrollment (Actual)

55

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10016
        • Bellevue Hospital
      • New York, New York, United States, 10016
        • NYU Langone Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • HIV infection
  • Current Antiretroviral Therapy with no change in regimen in the 12 weeks prior to study entry and no plans to change ART for the study duration
  • Ability to sign consent and comply with the protocol

Exclusion Criteria:

  • Known CD4+ T cell counts < 200 cells/mm3 during the 6 months prior to study entry
  • Established cardiovascular disease (thereby necessitating antiplatelet therapy)
  • NSAID use in the past week (including aspirin)
  • Unable to be off NSAIDs for the duration of the trial
  • Any antiplatelet or antithrombotic use
  • Allergy to aspirin or clopidogrel
  • Pregnancy
  • Chronic kidney disease (GFR<45 ml/min)
  • AIDS
  • Active drug or alcohol use that would interfere with adherence to study requirements
  • Any known bleeding disorder
  • Use of regularly prescribed medication such as steroids, or immunosuppressive agents
  • Known anemia (Hb <8mg/dL)
  • Thrombocytopenia (platelet count <75) or thrombocytosis (Platelet count >600)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: SINGLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
NO_INTERVENTION: Control
This arm of 10 subjects will be assigned randomly via a computer generated treatment sequence, and then be given no antiplatelet medication.
ACTIVE_COMPARATOR: Aspirin
This arm of 20 subjects will be assigned randomly via a computer generated treatment sequence, and then be given aspirin.
Drug: Aspirin
ACTIVE_COMPARATOR: Clopidogrel
This arm of 20 subjects will be assigned randomly via a computer generated treatment sequence, and then be given clopidogrel.
Drug: Clopidogrel

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage Platelet Aggregation in PRP After Stimulation With Arachidonic Acid 1600 μM for 5 Min
Time Frame: Baseline, 14 Days
The primary objective of these analyses will be to compare the effects of aspirin versus control and clopidogrel versus control for the outcome of platelet activity. Aspirin is expected to decrease arachidonic acid-induced platelet aggregation by 50% versus control. Clopidogrel is expected to decrease ADP-induced platelet aggregation by 50% versus control.
Baseline, 14 Days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage Platelet Aggregation in PRP After Stimulation With ADP 5μM for 5 Min
Time Frame: Baseline, 14 Days
Baseline, 14 Days
Percentage Monocyte-Platelet Aggregates
Time Frame: 14 Days
Secondary objectives will compare the effect of each antiplatelet therapy drug on biomarkers related to inflammation
14 Days
Percentage Monocyte-Platelet Aggregates
Time Frame: 14 Days
Secondary objectives will compare the effect of each antiplatelet therapy drug on biomarkers related to immune activity
14 Days
Percentage Leukocyte-Platelet Aggregate
Time Frame: 14 Days
Secondary objectives will compare the effect of each antiplatelet therapy drug on biomarkers related to endothelial function.
14 Days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

NYU Langone Health

Investigators

  • Principal Investigator: Jeffrey S Berger, MD, NYU School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

February 1, 2015

Primary Completion (ACTUAL)

April 1, 2016

Study Completion (ACTUAL)

February 1, 2017

Study Registration Dates

First Submitted

March 10, 2015

First Submitted That Met QC Criteria

September 22, 2015

First Posted (ESTIMATE)

September 24, 2015

Study Record Updates

Last Update Posted (ACTUAL)

October 15, 2018

Last Update Submitted That Met QC Criteria

September 13, 2018

Last Verified

September 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 14-02104

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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